Phosphoric Acid → 4-Nitro-1,3-dihydro-2H-indol-2-one

Temperature

70 °C

A mixture of 4-nitroindole (12.2 g, 75.2 mmol) and N-chlorosuccinimide (6.07 g, 30.1 mmol) in CHCl3 (500 mL) was heated at reflux for 30 h, then concentrated under reduced pressure to give an orange solid. The solid was dissolved in AcOH (200 mL) and the resulting solution was warmed to 70° C., then 85% H3PO4 (80 mL) was added over 2 min. The mixture was heated to reflux for 90 min then cooled on ice. The cooled mixture was adjusted to pH 6 by addition of 10 N NaOH (450 mL), followed by aqueous NaHCO3, keeping the temperature below 30° C. The mixture was extracted with EtOAc (3×1 L) and the combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was partially purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—100:0 to 0:100, and then triturated with MeOH to give the title compound. MS: m/z 179 (M+1).

1. temperaturewas heated
2. temperatureat reflux for 30 h
3. concentrationconcentrated under reduced pressure
4. customto give an orange solid
5. temperatureThe mixture was heated
6. temperatureto reflux for 90 min
7. temperaturethen cooled on ice
8. customthe temperature below 30° C
9. extractionThe mixture was extracted with EtOAc (3×1 L)
10. dry with materialthe combined organic extracts were dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe crude product was partially purified by silica gel chromatography
14. washeluting with a gradient of hexane
15. customEtOAc—100:0 to 0:100, and then triturated with MeOH

ORD record

ord-100f6940ca6f4169bc4a6ba47e40ae6b

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07968540B2